P1088: UPDATED DATA FROM A PHASE 1/2 STUDY OF BRENTUXIMAB VEDOTIN COMBINED WITH CHEMOTHERAPY IN PEDIATRIC PATIENTS WITH ADVANCED STAGE CLASSICAL HODGKIN LYMPHOMA
Authors: F. Locatelli, F. Luisi, M. Pianovski, M. A. Salvino, F. Fagioli, S. Epelman, L. Britto De Abreu Lima, R. Norris, V. Odone Filho, M. Zecca, C. Favre, R. Kobayashi, Y. Koga, Y. Sidi, X. Zhou, X. Bai, F. Campana, E. J. Leonard, A. R. Franklin
Journal: HemaSphere (2022)

Background: Brentuximab vedotin is a CD30-directed monoclonal antibody-drug conjugate approved for use in the first-line adult classical Hodgkin lymphoma (cHL) setting in combination with doxorubicin, vinblastine, and dacarbazine (A+AVD). The safety, tolerability, recommended dosing, immunogenicity, and antitumor activity of A+AVD have not previously been evaluated as a first-line therapy in treatment-naïve pediatric patients with cHL. Aims: To provide updated safety and efficacy data from an open-label phase 1/2 study of A+AVD in previously untreated pediatric patients with stage III or IV cHL (NCT02979522). Methods: Patients with newly diagnosed stage III or IV cHL who were aged 5 to <18 years were treated with A+AVD on days 1 and 15 of 28-day cycles, for a maximum of 6 cycles. In phase 1, patients (n = 8) received brentuximab vedotin 48 mg/m2 + AVD; dose-limiting toxicity (DLT) was assessed from day 1 of cycle 1 to day 56. In phase 2, 51 additional patients received the same treatment regimen. Progression-free survival (PFS) was defined as the time between first dose and time of disease progression, and event-free survival (EFS) was defined as the time between first dose and time of treatment failure; EFS events were disease progression, treatment withdrawal, and death. All patients had been on study for at least 2 years at the data cutoff (September 24, 2021). The data presented refer to phases 1 and 2 combined. Results: All patients (n = 59) in phases 1 and 2 completed 6 cycles of A+AVD. Among 6 DLT-evaluable patients in phase 1, no DLTs were observed. The maximum tolerated dose of brentuximab vedotin was not reached and the recommended dose was determined to be 48 mg/m2. Treatment-emergent adverse events (TEAEs) occurred in all patients; the most common TEAEs were vomiting (85%), nausea (75%), and neutropenia (58%). Fourteen patients (24%) experienced treatment-emergent peripheral neuropathy (PN); of these, 10 patients had PN resolved by end of treatment (EOT), 13 patients had PN resolved by last contact, and one patient had ongoing grade 1 paraesthesia at last contact. No on-study deaths occurred. At the end of cycle 2, the PET-negative rate (Deauville score 1, 2, or 3) was 90%. Objective response rate (complete response [CR] + partial response) according to independent review facility was 88%, with 76% of patients achieving a CR. Median duration of response and duration of CR were not estimable. Median PFS, EFS, and overall survival were not reached, suggesting promising efficacy of A+AVD in pediatric patients. Overall PFS, EFS and overall survival data will be presented at the meeting. Summary/Conclusion: Brentuximab vedotin 48 mg/m2 plus AVD every two weeks was generally well tolerated with an acceptable safety profile, and demonstrated an efficacy benefit in CD30+ pediatric patients with previously untreated advanced cHL. These data support A+AVD as a suitable frontline therapy option in this patient population.